Tag Archives: meningitis

Root Cause

FDA Inspections Find Issues at Compounding Pharmacies

By Kim Smiley

Unsafe practices at compounding pharmacies were found during recent Federal Drug Agency (FDA) inspections.  The FDA visited about 30 pharmacies in 18 different states, focusing on the production of sterile drugs which was determined to be the highest risk to patient safety.   The inspection findings include a number of potential contamination issues such as inadequate ventilation, unidentified particles in vials of supposedly sterile medications, cleanliness issues in clean rooms such as rust and mold, and insufficient microbiological testing. Interest in compounding pharmacies was increased after the fall 2012 outbreak of fungal meningitis that killed 50 and sickened hundreds was traced back to compounded injectable steroid medication that had been shipped across the country.

A root cause analysis of the issues at compounding pharmacies can be done by building a Cause Map.  A Cause Map visually lays out the different causes that contribute to an issue and is a way to intuitively illustrate the problem.  Compounding medications are an issue because they can pose both indirect and direct risks to patient safety and patients are using them.   The indirect risk is that patients may inadvertently use an ineffective medication.  Compounded medications are not regulated by the FDA and have not gone through a formal approval process that requires extensive testing.  Medications that are compounded can also be a direct risk to patient safety if they are contaminated or sub- or super-potent.  As the fatal fungal meningitis outbreak unfortunately demonstrated, contamination of supposedly sterile drugs can have deadly consequences. Compounded drugs are receiving more attention than traditionally manufactured drugs because some of the facilities may have less oversight and the recent investigations found more issues with the work processes at the compounding pharmacies than is typically discovered at drug manufacturing facilities.

Many are asking questions about how compounding pharmacies are regulated and overseen.  Compared to drug manufacturers, the FDA’s regulatory authority over compounding pharmacies is limited.  Compounding pharmacies are not generally even required to inform the FDA what drugs they are making or register with the FDA.  State boards of pharmacy regulate the compounding pharmacies and the FDA typically becomes involved only to do for-cause inspections upon receiving reports or complaints or when states have requested assistance.

It’s worth noting that compounding pharmacies do serve an important need.  Some individuals cannot be treated with standard manufactured medication.  An example of this is when somebody is allergic to an inactive ingredient, such as a dye, in an approved medication.  The real concern is that the creation and  use of compounded medications seems to be changing from its traditional function.  According to Ilisa Bernstein, acting director of Center for Drug Evaluation and Research’s Office of Compliance, “Some aspects of these firms’ operations appear more consistent with those of drug manufacturers than with those of traditional pharmacies. Some firms make large amounts of drugs that appear to be copies of FDA-approved, commercially available drugs when it does not appear that there is a medical need for an individual patient to receive a compounded version of the drug.”

There have been a number of voluntarily recalls as a result of the recent inspections.  The FDA and state regulatory boards are working together to address the issues that were uncovered.  Additionally, the FDA is pushing for new legislative authority over the highest-risk compounding pharmacies, but there isn’t agreement on whether changes are necessary and it’s not clear what the outcome will be.

For more information about compounded medications, please visit the FDA website.

Root Cause

Update: Contaminated Injections Have Now Killed 29

By ThinkReliability Staff

In a previous blog, we discussed deaths related to fungal meningitis believed to have resulted from fungal contamination of a compounded drug used as an injection for back pain.  Sadly, since our last post, the numbers of deaths and injuries has risen.  So far, 29 patients have been killed and more than 360 have been sickened by the infected injections.  Because drugs from the three affected lots were injected for pain relief to approximately 14,000 patients, investigators expect to see many more cases in the coming months.  Some of these patients received injections in other joints, so they are suffering from peripheral joint infection, which is less severe and less likely to lead to death than fungal meningitis.

We can update the Cause Map, or visual root cause analysis, which was started in our previous blog.  Specifically, as investigators are able to provide more detail about the case, we can update causes and validate them with evidence.  We are also able to update the outline as more patient deaths and sickness are discovered.

Investigators have verified that the source of the fungal contamination was the compounding company.  They noted in investigations that the clean room was contaminated due to lack of control of the humidity and temperature.  It appears that the air conditioning was shut down at night, resulting in environmental issues. Additionally, sterilization at the company was found to be inadequate.  Sterilization procedures were not followed, and sterilization equipment was found to be contaminated, possibly because it was not properly tested.  Once the contamination made it into the drug, the drug was shipped without the company knowing of the contamination, because shipping on some lots took place before the results of sterility testing were received.

The Massachusetts Department of Health has announced increased oversight of compounding companies, including annual inspections.  A bill has been introduced in Congress for FDA regulation of compounding companies that produce larger quantities of drugs for mass distribution, as appears to be the case in this instance.  It also recommends requiring compounded drugs to contain a label stating they have not been FDA-approved.  Although the compounding company responsible for the contamination has been closed down, it is hoped that a higher level of regulation will reduce the possibility of similar deaths in the future.

To view the updated Outline and Cause Map, please click “Download PDF” above.  Or click here to read more.

Root Cause

Contaminated Injections Kill 5

By ThinkReliability Staff

At least 35 patients have come down with rare fungal meningitis after an injection they received for back pain was contaminated with fungus. Five have died so far. Because of the severity of the disease and the long incubation period, more cases – and more deaths – are expected in the coming months.

We can examine the issues related to the fungal meningitis in a Cause Map, or visual root cause analysis. Documenting the causes visually can make a complex medical issue easier to understand. We begin with the impacts to the goals. The deaths and severe sickness are an impact to the patient safety goal. While we begin with the known cases, these numbers can be updated if more cases are discovered. The compounding company which prepared the injections has voluntarily surrendered its license, an impact to the compliance goal and has recalled 3 lots of the drug used in the injection (methylprednisolone acetate), which can be considered an impact to both the organizational and property goal. The extremely difficult treatment ahead of these patients (estimated to take months) is an impact to the patient services and labor goal. The contamination of the injection itself can be considered an environmental goal.

Once we have captured these impacted goals, we can begin with the focus of our investigation – the patient safety goal – and ask “why” questions to develop the cause-and-effect relationships that resulted in the disease. The patient deaths and sickness are due to contraction of fungal meningitis. These patients came down with fungal meningitis because fungus was introduced to their nervous system. The injections that the patients received for back pain were injected epidurally, which allows access to the nervous system, and were infected with aspergillus, a common fungi. More testing is being done to determine whether the contamination was in the drug within the injection, or the numbing agent or antiseptic wipes being used. Due to the widespread (across several states) outbreak, it is believed that the drug within the injection is to blame, but because of the seriousness of this issue, all potential causes are being carefully tested.

Because the drug used in the injection was compounded, the contamination could have occurred within a raw ingredient used in the compounding, or it could have become contaminated during the compounding process. The source of the outbreak is not yet known, but because compounded drugs and compounding companies receive less oversight than drug manufacturers, it is suspected that the contaminant was introduced during the compounding process.

Initial symptoms of fungal meningitis are subtle, including headache, fever, dizziness, nausea and slurred speech. The symptoms can take up to a month from introduction of the fungus to appear. If patients have received a shot for back pain, they should contact their doctor to see if it was from the infected lot. Early and immediate treatment is important.

To view the Outline and Cause Map, please click “Download PDF” above. Or click here to read more.